Explore the vast range of titles available.

Background and Objectives: Hepatic encephalopathy (HE) management becomes particularly challenging in older patients. This study aimed to evaluate the physician-reported diagnostic approaches, therapeutic strategies, and specific challenges in managing HE in older cirrhotic patients across Italy. Methods: A nationwide survey was conducted under the aegis of the Italian Association for the Study of the Liver (AISF). Forty-three hepatology centres participated. Data were analyzed using descriptive statistics. Results: Participating centers followed over 6000 older patients with cirrhosis, nearly one-third of whom experienced overt HE and/or minimal HE episodes in the previous year. Physicians reported that infections were the most frequently reported precipitating factor, followed by constipation and electrolyte disturbances for OHE. Half of patients with HE (50%; IQR 30.0–50.0%) experienced recurrent episodes, while 22% (IQR 10.0–30.0%) were reported to have persistent HE. In this setting, the diagnosis of HE was often complicated by cognitive decline. Treatment primarily consisted of a combination of lactulose and rifaximin, but adherence was often limited. Caregiver support emerged as a critical element in patient management. The management of comorbidities such as diabetes and chronic kidney disease was a major challenge, and nutritional screening was not routinely implemented across centres. Conclusions: This study highlights the need for better multidisciplinary management, improved caregiver support, and more consistent approaches to the diagnosis and treatment of HE in the elderly. The survey also explored how centres approach the differential diagnosis between HE and age-related cognitive disorders, the practical role of caregivers in outpatient management, and the impact of comorbidities, polypharmacy, and nutritional issues on everyday care. Marked heterogeneity emerged in psychometric assessment, multidisciplinary collaboration, and nutritional screening, indicating that several relevant aspects of care remain insufficiently standardized. Overall, the findings suggest that older patients with HE should be regarded as a distinct high-risk subgroup requiring tailored diagnostic pathways and integrated management models.

In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood proinflammatory cytokines, while Ruminococcaceae and SCFAs played a protective role. Within the peripheral blood and faeces, certain species ( Stenotrophomonas pavanii , Methylobacterium extorquens ) and metabolites (methanol, threonine) were positively related to HE. Cirrhotic patients thus harbour a ‘functional dysbiosis’ in the faeces and peripheral/portal blood, with specific keystone species and metabolites related to clinical markers of systemic inflammation and HE.

Hepatic encephalopathy (HE) is a major problem in patients treated with TIPS. The aim of the study was to establish whether pre-TIPS covert HE is an independent risk factor for the development of HE after TIPS. Eighty-two consecutive cirrhotic patients submitted to TIPS were included. All patients underwent the PHES to identify those affected by covert HE before a TIPS. The incidence of the first episode of HE was estimated, taking into account the nature of the competing risks in the data (death or liver transplantation). Thirty-five (43%) patients developed overt HE. The difference of post-TIPS HE was highly significant (P=0.0003) among patients with or without covert HE before a TIPS. Seventy-seven percent of patients with post-TIPS HE were classified as affected by covert HE before TIPS. Age: (sHR 1.05, CI 1.02-1.08, P=0.002); Child-Pugh score: (sHR 1.29, CI 1.06-1.56, P=0.01); and covert HE: (sHR 3.16, CI: 1.43-6.99 P=0.004) were associated with post-TIPS HE. Taking into consideration only the results of PHES evaluation, the negative predicting value was 0.80 for all patients and 0.88 for the patients submitted to TIPS because of refractory ascites. Thus, a patient with refractory ascites, without covert HE before a TIPS, has almost 90% probability of being free of HE after TIPS. Psychometric evaluation before TIPS is able to identify most of the patients who will develop HE after a TIPS and can be used to select patients in order to have the lowest incidence of this important complication.

Muscle depletion is frequently encountered in cirrhotic patients. As muscle may represents an alternative site of ammonia detoxification in liver diseases, our study was aimed at investigating whether a decrease in muscle mass or function may independently influence the prevalence of neurocognitive alterations in cirrhosis. Three-hundred consecutive hospitalized cirrhotic patients were prospectively enrolled. Liver function, a complete neurocognitive assessment for the diagnosis of clinical or subclinical hepatic encephalopathy (HE) and parameters of nutritional status and muscle function were evaluated in each patient at admission. Clinically overt HE, at admission or in the last 12 months, or a diagnosis of minimal HE were significantly higher in cirrhotic patients with muscle depletion or decreased muscle strength. The fasting venous blood ammonia concentrations were also higher in this group. Muscle depletion was an independent risk factor at multivariate analysis both for overt and minimal HE. In conclusion cirrhotic patients with muscle depletion are at higher risk of HE and the amelioration of nutritional status is a possible goal to decrease the prevalence of neurocognitive alterations in these patients.

IntroductionMyosteatosis, characterised by altered muscle composition detectable by muscle radiodensity attenuation on CT scans, has been associated with increased mortality in patients with cirrhosis. However, standard attenuation cut-offs, derived primarily from oncology populations, may not be appropriate for patients with cirrhosis. This study protocol aims to address this diagnostic gap by validating the Ebadi cut-offs, which are based on a retrospective cohort and have not been extensively validated in a cirrhotic population. The aim of the study is to refine these cut-offs for more accurate prediction of mortality in patients with cirrhosis using two independent patient cohorts (retrospective and prospective).Methods and analysisThis post hoc validation study analyses muscle weakness cut-offs in patients with cirrhosis using data from two independent cohorts. A total of 1537 patients will be analysed. The study will assess interobserver variability to ensure robust results by analysing random samples of 60 patients from the two cohorts. Statistical methods will be used to determine the accuracy and relevance of current cut-offs in predicting patient mortality. The analysis will also examine the relationship between muscle wasting and clinical outcomes in cirrhosis and the relationship with muscle mass loss.Ethics and disseminationEthical approval for this study has been obtained from the relevant institutional review boards. The results will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals. The results of the study are expected to contribute to improved diagnostic criteria for myosteatosis in cirrhosis, providing clinicians with more tailored and accurate tools for cirrhosis prognosis.Trial registration number NCT06593015.

The spread of multi-resistant infections represents a continuously growing problem in cirrhosis, particularly in patients in contact with the healthcare environment. Our prospective study aimed to analyze epidemiology, prevalence and risk factors of multi-resistant infections, as well as the rate of failure of empirical antibiotic therapy in cirrhotic patients. All consecutive cirrhotic patients hospitalized between 2008 and 2013 with a microbiologically-documented infection (MDI) were enrolled. Infections were classified as Community-Acquired (CA), Hospital-Acquired (HA) and Healthcare-Associated (HCA). Bacteria were classified as Multidrug-Resistant (MDR) if resistant to at least three antimicrobial classes, Extensively-Drug-Resistant (XDR) if only sensitive to one/two classes and Pandrug-Resistant (PDR) if resistant to all classes. One-hundred-twenty-four infections (15% CA, 52% HA, 33% HCA) were observed in 111 patients. Urinary tract infections, pneumonia and spontaneous bacterial peritonitis were the more frequent. Forty-seven percent of infections were caused by Gram-negative bacteria. Fifty-one percent of the isolates were multi-resistant to antibiotic therapy (76% MDR, 21% XDR, 3% PDR): the use of antibiotic prophylaxis (OR = 8.4; 95%CI = 1.03-76; P = 0,05) and current/recent contact with the healthcare-system (OR = 3.7; 95%CI = 1.05-13; P = 0.04) were selected as independent predictors. The failure of the empirical antibiotic therapy was progressively more frequent according to the degree of resistance. The therapy was inappropriate in the majority of HA and HCA infections. Multi-resistant infections are increasing in hospitalized cirrhotic patients. A better knowledge of the epidemiological characteristics is important to improve the efficacy of empirical antibiotic therapy. The use of preventive measures aimed at reducing the spread of multi-resistant bacteria is also essential.

Alcohol‐related liver disease (ArLD) is a major cause of chronic liver disease globally. Traditionally, ArLD was mostly a concern in men rather than in women; however, such a sex gap is rapidly narrowing due to increasing chronic alcohol consumption among women. Female sex is more vulnerable to the harmful effects of alcohol with a higher risk of progression to cirrhosis and development of associated complications. The relative risk of cirrhosis and liver‐related mortality is significantly higher in women than in men. Our review endeavors to summarize the current knowledge on sex differences in alcohol metabolism, pathogenesis of ArLD, disease progression, indication for liver transplant and pharmacological treatments of ArLD, and provide evidence in support of a sex‐specific management of these patients.

BACKGROUND:Hepatic encephalopathy (HE) is the major complication of transjugular intrahepatic portosystemic shunt (TIPS). In cirrhotic patients, a correlation between sarcopenia and hepatic encephalopathy has been suggested.AIM:to evaluate the evolution of the skeletal muscle quantity and quality at CT scan and of the patients' cognitive impairment (both overt and minimal HE) before and after TIPS.PATIENTS AND METHODS:27 cirrhotic patients submitted to TIPS were studied. The modification of Skeletal Muscle Index (SMI), muscle attenuation, HE and plasma ammonia were evaluated before and after a mean follow-up of 9.8 ± 4 months after TIPS.RESULTS:During the follow-up, the mean SMI and muscle attenuation increased significantly, although not uniformly in all patients. PHES (Psychometric Hepatic Encephalopathy Score) and ammonia improved significantly in the patients with amelioration in SMI >10% (n = 16) and not in those without (n = 11) (PHES: −1.6 ± 2 vs −4.8 ± 2.1; P = 0.0005; ammonia: 48.5 ± 28.7 vs 96 ± 31.5 μg/dl; P = 0.0004). Moreover, the prevalence of minimal HE (12.5% vs 73%, P = 0.001) as well as the number of episodes of overt HE during the follow-up were significantly reduced in the patients with improved SMI. MELD remained stable or worsened after TIPS and was not significantly different between the groups with or without SMI improvement.CONCLUSION:The amelioration of muscle wasting and HE independent of liver function observed after TIPS supports the causal relationship between muscle wasting and HE.

BACKGROUND:Muscle alterations (myosteatosis and sarcopenia) are frequent in cirrhosis and related to some complications included overt hepatic encephalopathy. The aim of our study was to investigate the relationship between muscle alterations and minimal hepatic encephalopathy (MHE) and their role on the risk of overt HE.METHODS:64 cirrhotics were submitted to Psychometric Hepatic Encephalopathy Score (PHES) and to Animal Naming Test (ANT) to detect MHE. CT scan was used to analyse the skeletal muscle index (SMI) and attenuation. The incidence of the first episode of HE, taking into account the competing risk nature of the data, was estimated.RESULTS:Myosteatosis was observed in 24 patients (37.5%), sarcopenia in 37 (58%) and MHE in 32 (50%). Both myosteatosis (62.5 vs 12.5%; P < 0.001) and sarcopenia (84 vs 31%; P < 0.001) were more frequent in patients with MHE. The variables independently associated to the presence of MHE were: sarcopenia, previous overt HE and myosteatosis. Thirty-one (48%) patients developed overt HE during 16.1 ± 13 months; myosteatosis was detected in 68% and sarcopenia in 84% of them. Sarcopenia and myosteatosis were also independently associated to the development of overt HE. Venous ammonia was significantly higher in sarcopenic patients (62.6 ± 17.7 vs 41.4 ± 16.1 μg/dl; P < 0.001) and in myosteatosic patients (65.2 ± 19.2 vs 46.7 ± 17.1 μg/dl; P < 0.001) and inversely correlated to both parameters. Survival was significantly lower in malnourished patients compared with patients without myosteatosis or sarcopenia (P < 0.001).CONCLUSIONS:Myosteatosis and sarcopenia, probably by reducing the handling of ammonia in the muscle, are independently associated to MHE and to the risk of overt HE in cirrhotics. In malnourished patients, the amelioration of nutritional status may be a possible goal to decrease both the prevalence oh MHE and the incidence of overt HE.